Faculty of Life and Environmental Sciences, University of Tsukuba, Japan.
The Baker Institute for Animal Health, Cornell University, Ithaca, NY, USA.
FEBS J. 2018 May;285(10):1827-1839. doi: 10.1111/febs.14449. Epub 2018 Apr 16.
Sperm entering the epididymis are immotile and cannot respond to stimuli that will enable them to fertilize. The epididymis is a highly complex organ, with multiple histological zones and cell types that together change the composition and functional abilities of sperm through poorly understood mechanisms. Sperm take up taurine during epididymal transit, which may play antioxidant or osmoregulatory roles. Cysteine dioxygenase (CDO) is a critical enzyme for taurine synthesis. A previous study reported that male CDO mice exhibit idiopathic infertility, prompting us to investigate the functions of CDO in male fertility. Immunoblotting and quantitative reverse transcription-polymerase chain reaction analysis of epididymal segments showed that androgen-dependent CDO expression was highest in the caput epididymidis. CDO mouse sperm demonstrated a severe lack of in vitro fertilization ability. Acrosome exocytosis and tyrosine phosphorylation profiles in response to stimuli were normal, suggesting normal functioning of pathways associated with capacitation. CDO sperm had a slight increase in head abnormalities. Taurine and hypotaurine concentrations in CDO sperm decreased in the epididymal intraluminal fluid and sperm cytosol. We found no evidence of antioxidant protection against lipid peroxidation. However, CDO sperm exhibited severe defects in volume regulation, swelling in response to the relatively hypo-osmotic conditions found in the female reproductive tract. Our findings suggest that epididymal CDO plays a key role in post-testicular sperm maturation, enabling sperm to osmoregulate as they transition from the male to the female reproductive tract, and provide new understanding of the compartmentalized functions of the epididymis.
精子进入附睾时没有运动能力，也无法对刺激做出反应，从而无法使其具备受精能力。附睾是一个高度复杂的器官，具有多个组织学区域和细胞类型，它们通过尚未完全了解的机制改变精子的组成和功能能力。精子在附睾转运过程中摄取牛磺酸，牛磺酸可能具有抗氧化或渗透调节作用。半胱氨酸双加氧酶（CDO）是牛磺酸合成的关键酶。先前的研究报告称，雄性 CDO 小鼠表现出特发性不育，这促使我们研究 CDO 在雄性生育力中的功能。附睾段的免疫印迹和定量逆转录聚合酶链反应分析显示，雄激素依赖性 CDO 表达在附睾头部最高。CDO 小鼠精子表现出严重缺乏体外受精能力。顶体反应和对刺激的酪氨酸磷酸化谱正常，表明与获能相关的途径正常发挥作用。CDO 精子头部异常略有增加。CDO 精子在附睾管腔内液和精子胞质溶胶中的牛磺酸和次牛磺酸浓度降低。我们没有发现针对脂质过氧化的抗氧化保护证据。然而，CDO 精子在体积调节方面存在严重缺陷，在女性生殖道中相对低渗的条件下会发生肿胀。我们的研究结果表明，附睾 CDO 在睾丸后精子成熟中发挥关键作用，使精子能够在从男性生殖道向女性生殖道过渡时进行渗透调节，并为附睾的分隔功能提供了新的认识。
